Francisella tularensis is one of a small group of bacteria recognized for their virulence and potential for use as biological weapons. In this study we utilize a novel approach to identify an immunologically prominent component of F. tularensis that appears to be a promising vaccine candidate. Francisella is an intracellular pathogen that infects cells of the reticuloendothelial system. Other bacteria, such as Brucella spp. have this part of their life cylce in common. However, while mice injected with Brucella spp. survive and produce antibodies to the bacteria which are immunologically reactive not only with Brucella spp. but, also with Francisella. When we vaccinated mice with a B. abortis O-linked polysaccharide (OPS) and then challenged them with 10 LD50F.tularensis LVS, 60% survived. Sera from Brucella OPS-primed/F.tularensis-challenged mice was used to identify immune reactive proteins from F. tularensis. A novel 52 kDa fraction was identified. While vaccination of mice with this partially purified fraction only provided 20% protection to F.tularensis challenged mice, both whole cell extracts and a partially purified soluble fraction (>30kDa) given to Brucella-vaccinated mice were 100% protective. The 52 kDa enriched fraction elicited a rudimentary cytokine burst of nitric oxide in a cell culture of J774.1 macrophages. The 52 kDa fraction was degraded by proteinase K and appeared to decrease in size to 36 kDa in the presence of DNAase, suggesting a possible protein and nucleic acid composition. The host response to F. tularensiss infection is complex, but given the ability of the 52 kDa component to protect against live vaccine challenge, and its apparent ability to elicit a cytokine burst, this component may have potential use in future vaccine production.

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en_US

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Lethbridge, AB : University of Lethbridge, Faculty of Arts and Science, 2003

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Thesis (University of Lethbridge. Faculty of Arts and Science)

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Dissertations, Academic

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Francisella tularensis -- Research

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Vaccines -- Biotechnology -- Research

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Tularemia -- Vaccination -- Research

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Identification of a vaccine candidate in protein extracts from francisella tularensis